The present invention relates to a novel pharmaceutical composition containing the base form of phenylephrine. Phenylephrine has the formula 3-hydroxy-.alpha.-[(methylamino)methyl]benzyl alcohol.
Phenylephrine is a well-known pharmaceutically active amine whose principal use in the field of ophthalmology is as a mydriatic. There are, however, certain known disadvantages associated with the use of phenylephrine as a mydriatic agent. Those disadvantages, involving systemic side effects, have limited the use of this highly effective drug. Thus, in spite of the fact that it is one of the most effective mydriatics available, its use is significantly limited because of the significant side effects which may occur in some individuals treated with phenylephrine. Those unwanted significant side effects range from hypertension, syncope, and even in some cases to myocardial infarction, leading to death.
Phenylephrine HCl is a very hydrophilic drug used in the eye for its mydriatic and capillary decongestion effects. Because of its hydrophilic characteristics, it poorly penetrates the epithelium of the cornea, therefore, a relatively high concentration, 2.5% or 10%, must be applied to the eye topically to achieve a potent effect. As a result of applying a large dose which is poorly absorbed, the earlier mentioned significant systemic side effects may occur. However, because phenylephrine is such an effective mydriatic agent, despite the potential risk of adverse side effects, there is a continuing need for its use. In the past there have been some attempts to prepare prodrugs of phenylephrine in order to minimize the side effect risk. While the preparation of prodrugs is often advantageous, it is not without is disadvantages from time to time. For example, there is an increased cost factor with the preparation of prodrugs of phenylephrine. Accordingly, it can be seen that there is a continuing and real need for a technique which allows one to use phenylephrine in a topical ocular dose form which maximizes mydriatic effectiveness so that lower levels of the active drug can be employed.
Clearly, then, there is a need to reduce the systemic side effects of phenylephrine. Theoretically this could be accomplished by increasing the ocular absorption and thereby reducing systemic absorption. However, the reduction in systemic side effects is an indirect effect of improved ocular absorption. This is exemplified by the fact that even though ocular absorption may double from 2 to 4%, systemic absorption decreases from 98% to only 96%, which is not a significant decrease with respect to systemic side effects. Nevertheless, by increasing the absorption two-fold, the dose can be reduced by one-half to achieve the same therapeutic effect and in this manner systemic effects can be reduced substantially.
This invention has as its primary objective the development of new and useful phenylephrine topical compositions which when used at mydriatically effective levels allow a lower dosage level to be instilled in the eye, leading to decreased side effect risk.
Another objective of the present invention is to provide a safe and pharmaceutically effective mydriatic which is a combination of phenylephrine in the base form and a vegetable oil carrier.
Yet another objective of the present invention is to prepare a mydriatic composition for topical ocular treatment, useful in ophthalmic diagnosis and surgery, which uses phenylephrine in the base form, allowing it to be more effectively absorbed than in the acid form.
Another objective of the present invention is to provide an ocular composition which will allow phenylephrine to be used in its base form to produce a local or systemic physiological effect, similar to that achieved by much higher concentrations of acid or salt forms of phenylephrine.
An even further objective is to develop a drug delivery system for phenylephrine, adopted to improve the drug absorption, and yet maintain drug potency.
The method and manner of accomplishing these and other objectives of the present invention will become apparent from the detailed description which will follow hereinafter.